Species differences nicotine

As mentioned in the previous section, we have observed greater impact of nicotine on locomotor activity in female than in male rats (Kanyt et al. 1999). The psychostimulant theory of addiction also proposes that the locomotor stimulant and rewarding effects of addictive drugs have a common neuronal substrate, although there are some studies that do not support this hypothesis (Carr et al. 1988 Villegier et al. 2006). Species differences or methodological differences in the studies may underlie the discrepancies. 

Strain differences in responses to nicotine are well documented in rodents, albeit these studies have concentrated on species differences using male animals (e.g., Collins et al. 1988). If there are strong strain differences in response to nicotine suggesting genetic vulnerability to or protection from nicotine addiction, sex is most likely another factor that could impact responses to nicotine as well. 

To what extent are the rodent models of nicotine physical dependence and nicotine withdrawal syndrome valid representations of physical dependence and withdrawal syndrome in hnman tobacco users Validity can only be partial at best because of species differences and differences in the means, dnration and composition of drug exposnre (nicotine alone versus tobacco smoke). The differences between the models and hnman tobacco use phenomena will always be as important as the analogies. 

There are no apparent species differences in nicotine toxicity between animals and man. The toxic sequelae following chronic nicotine exposure to animals is similar to that in man including GI problems, cardiovascular effects, changes in neurochemistry, and reproductive effects such as decreased birth weight and length of gestation. 

Another possible target for toxins are the receptors for neurotransmitters since such receptors are vital, especially for locomotion. In vertebrates the most strategic receptor is that for acetylcholine, the nicotinic receptor. In view of the breadth of action of the various conotoxins it is perhaps not surprising that alpha-conotoxin binds selectively to the nicotinic receptor. It is entirely possible that similar blockers exist for the receptors which are vital to locomotion in lower species. As mentioned previously, lophotoxin effects vertebrate neuromuscular junctions. It appears to act on the end plate region of skeletal muscle (79,59), to block the nicotinic receptor at a site different from the binding sites for other blockers (81). 

The demetalating abilities of buffer species depend on both their structures and their acidities. Thus, while pyridine-2-carboxylic (picolinic) acid catalyzes the demetalation even of the rather inert lm, its 3- and 4-isomers (nicotinic and isonicotinic acids) are inactive. The difference is rationalized to result from the ability that only coordinated picolinic acid has to deliver a proton to an amidato nitrogen in an intramolecular manner. The reaction order in picolinic acid equals one for la and two for lm. For lm, inactive pyridine and nicotinic acid speed up the demetalation in the presence of picolinic acid (Fig. 8). 

In this scheme, M <1 and K equilibrium constants. Direct binding experiments have confirmed the generality of this scheme for nicotinic receptors. Thus, distinct conformational states govern the different temporal responses that ensue upon addition of a ligand to the nicotinic receptor. No direct energy input or covalent modification of the receptor channel is required. 

Van den Beukel I, van Kleef RGDM, Oortgiesen M. Differential effects of physostigmine and organophosphates on nicotinic receptors in neuronal cells of different species. NeuroToxicol. 19(6) 777-788, 1998. 

Stewart J (1983) Conditioned and unconditioned drug effects in relapse to opiate and stimulant drug-administration. Prog Neuropsychopharmacol Biol Psychiatry 7 591-597 Stolerman IP (1988) Characterization of central nicotinic receptors by studies on the nicotine cue and conditioned taste aversion in rats. Pharmacol Biochem Behav 30 235-242 Stolerman IP (1989) Discriminative stimulus effects of nicotine in rats trained under different schedules of reinforcement. Psychopharmacology 97 131-138 Stolerman IP (1999) Inter-species consistency in the behavioural pharmacology of nicotine dependence. Behav Pharmacol 10 559-580... 

Interspecific differences are also known for some naturally occurring poisons. Nicotine, for instance, is used as an insecticide and kills many insect pests at low doses, yet tobacco leaves constitute a normal diet for several species. As indicated earlier, most strains of rabbit eat Belladonna leaves without ill effects, whereas other mammals are easily poisoned. Natural tolerance to cyanide poisoning in millipedes and the high resistance to the powerful axonal blocking tetrodotoxin in puffer fish are examples of the tolerance of animals to the toxins they produce. 

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